Five academic institutions, two governmental institutes and two leading SMEs, from Europe, Africa and Latin America, are joining forces to develop novel drugs against parasites. The 4-year EU-funded project led by VU University Amsterdam is called PDE4NPD: PhosphoDiEsterase inhibitors to target Neglected Parasitic Diseases.

Standstill in neglected parasitic disease treatment

Neglected parasitic diseases (NPDs) form an enormous obstacle to the development of communities across the world. The diseases are classified as ‘neglected’ as investments in finding cures for these illnesses are extremely low, especially when considering their devastating impact on human and veterinary health. The NPDs addressed in this project – Chagas disease, human African Trypanosomiasis, Leishmaniasis and Schistosomiasis – collectively result in 6.6 million disability-adjusted life years.

During the last 30 years, only 9 new drugs targeting these NPDs have come to market. Some of these treatments cause severe side effects, while others are very expensive or are threatened by drug resistance issues. One cause for this standstill is the lack of sufficient financial incentive due to the low return on investment in these diseases from the perspective of the pharmaceutical industry. A paradigm shift in policy and a substantial joint effort to address this discovery gap is urgently required.

Drug discovery platform

The PDE4NPD project enables both public and private partners to join forces within a EU Seventh Framework program to tackle these widely acknowledged healthcare needs. The consortium consists of VU University Amsterdam (NL), University of Glasgow (UK), University of Kent (UK), University of Antwerp (BE), The Spanish National Research Council (ES), Fundacao Oswaldo Cruz (BR), Theodor Bilharz Research Institute (EG), European Screening Port (DE), IOTA Pharmaceuticals (UK) and Top Institute Pharma (NL) and combines various drug discovery approaches into one platform that is dedicated to developing drugs against parasite phosphodiesterases (PDEs): a family of well¬-characterized enzymes.

“Previous studies have shown that targeting parasite PDEs is a viable strategy to combat parasitic disease and that PDEs are highly druggable”, states principal investigator Rob Leurs of VU University, “as well-known drugs such as Viagra® and Daxas® effectively target diseases caused by human PDEs”, continuing:

“This consortium has all the expertise to develop parasite‐specific PDE inhibitors with high clinical potential, especially the state-of-the-art structural biology and screening technologies required for finding new molecules with drug-like properties.”

“In parallel, our team of parasitology research groups will perform phenotypic screening on various parasites to identify substances that will kill the parasites. The consortium will further develop those compounds that demonstrate anti-parasitic activity working through PDE as the key drug target”, comments Leurs, adding: “Ultimately, PDE4NPD will develop into a generic platform in which any parasite PDE can enroll. The integrative approach allows the accumulation of fundamental knowledge with an efficiency that is typical for approaches that revolve around one target.”

Role of IOTA Pharmaceuticals Ltd

IOTA Pharmaceuticals, a company based in Cambridge, UK, has been performing research on NPDs for over 5 years and was part of an earlier team of companies targeting Trypanosomiasis. “IOTA’s drug discovery platform centers on a technique called fragment-based drug discovery (FBDD), which we have developed in association with our collaborators at VU University Amsterdam. With FBDD, we first identify small chemical fragments that bind to different parts of the therapeutic target, in this case a phosphodiesterase. Then, we elaborate these fragments into a larger compound with higher affinity for the target”, explains Dr Paul England, head of IOTA’s drug screening operations, adding: “We look forward to working closely with the other members of the PDE4NPD consortium to produce medicines to eradicate these devastating diseases”.